6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)>ethyl>-4(R)-<(tert-butyldimethylsilyl)oxy>-3,4,5,6-tetrahydro-2H-pyran-2-one | 127343-17-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)>ethyl>-4(R)-<(tert-butyldimethylsilyl)oxy>-3,4,5,6-tetrahydro-2H-pyran-2-one
• 英文别名: 6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphth-1(S)-yl>ethyl>-4(R)-(tert-butyldimethylsiloxy)-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-5(R)-hydroxy-6(R)-methyl-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)]ethyl]-4(R)-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-5(R)-hydroxy-,1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)]ethyl]-4(R)-tert-butyldimethylsilyloxy-3,4,5,6,-tetrahydro-2H-pyran-2-one；6(R)-(2-{8(S)-[(2,2-dimethylbutyryl)oxy]-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)}ethyl)-4(R)-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one；(1S,3R,4R,4aR,7S,8S,8aR)-8-(2-((2R,4R)-4-((tert-Butyldimethylsilyl)oxy)-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-4-hydroxy-3,7-dimethyldecahydronaphthalen-1-yl 2,2-dimethylbutanoate；[(1S,3R,4R,4aR,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-hydroxy-3,7-dimethyl-1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl] 2,2-dimethylbutanoate
• CAS: 127343-17-3
• 化学式: C₃₁H₅₆O₆Si
• 分子量: 552.868
• InChiKey: LAUDYRYMHPAVSG-KZOZDCKGSA-N

物化性质

• 沸点：
  598.9±50.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.89
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)>ethyl>-4(R)-<(tert-butyldimethylsilyl)oxy>-3,4,5,6-tetrahydro-2H-pyran-2-one 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以77%的产率得到丁酸,2,2-二甲基-,(1S,3R,4R,4aR,7S,8S,8aR)-十氢-4-羟基-3,7-二甲基-8-[2-[(2R,4R)-四氢-4-羟基-6-羰基-2H-吡喃-2-基]乙基]-1-萘基酯
  参考文献：
  名称：

  3-羟基-3-甲基戊二酰辅酶a还原酶抑制剂。7.辛伐他汀的六氢萘部分的修饰：5-氧化的和5-氧杂的衍生物。

  摘要：

  通过氧合和氧杂取代对辛伐他汀2a中的六氢萘环5位进行修饰，得到了两个衍生物系列，分别在体外评估了对3-羟基-3-甲基戊二酰辅酶A还原酶的抑制作用，并在体内急性评估了其作为α-羟色胺抑制剂的口服效果大鼠的胆固醇生成。在选择用于进一步生物学评估的化合物中，3,4,4a，5-四氢2a的6个β-甲基-5-氧杂10和5个α-羟基16衍生物，以及16个的6个β-表观异构体14证明在胆甾醇胺引发的狗中作为降胆固醇药具有口服活性。随后在狗中进行的急性口腔新陈代谢研究表明，化合物14和16的峰值血浆药物活性和曲线下面积值比化合物10低，并导致选择14和16进行毒理学评估。

  DOI：

  10.1021/jm00112a027
• 作为产物：
  描述：

  2,2-Dimethyl-butyric acid (1S,3R,4aS,7S,8S,8aS)-4a-bromo-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-3,7-dimethyl-4-oxo-decahydro-naphthalen-1-yl ester 在 sodium tetrahydroborate 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.58h， 生成 6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)>ethyl>-4(R)-<(tert-butyldimethylsilyl)oxy>-3,4,5,6-tetrahydro-2H-pyran-2-one
  参考文献：
  名称：

  3-羟基-3-甲基戊二酰辅酶a还原酶抑制剂。7.辛伐他汀的六氢萘部分的修饰：5-氧化的和5-氧杂的衍生物。

  摘要：

  通过氧合和氧杂取代对辛伐他汀2a中的六氢萘环5位进行修饰，得到了两个衍生物系列，分别在体外评估了对3-羟基-3-甲基戊二酰辅酶A还原酶的抑制作用，并在体内急性评估了其作为α-羟色胺抑制剂的口服效果大鼠的胆固醇生成。在选择用于进一步生物学评估的化合物中，3,4,4a，5-四氢2a的6个β-甲基-5-氧杂10和5个α-羟基16衍生物，以及16个的6个β-表观异构体14证明在胆甾醇胺引发的狗中作为降胆固醇药具有口服活性。随后在狗中进行的急性口腔新陈代谢研究表明，化合物14和16的峰值血浆药物活性和曲线下面积值比化合物10低，并导致选择14和16进行毒理学评估。

  DOI：

  10.1021/jm00112a027

文献信息

• 5-oxygenated HMG-CoA reductase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US04963538A1

  公开（公告）日：1990-10-16

  Novel HMG-CoA reductase inhibitors are useful as antihypercholesterolemic agents and are represented by structural formulae (I) or (II): ##STR1## wherein position 5 of the polyhydronaphthyl ring is singly or doubly bonded to oxygen or incorporated into a C.sub.3-7 carbocyclic ring.

  新型HMG-CoA还原酶抑制剂可作为抗高胆固醇药物，其结构式为(I)或(II)：##STR1##其中多氢萘环的第5位与氧原子单键或双键结合，或者并入到一个C.sub.3-7碳环中。
• Intermediates and processes in the preparation of 5-oxygenated HMG-COA
  申请人：Merck & Co., Inc.

  公开号：US04921974A1

  公开（公告）日：1990-05-01

  This invention relates to novel intermediates and novel processes for their preparation where said intermediates are useful in the preparation of 5'-oxygenated derivatives (I) of lovastation and analogs thereof at the 8'-acyl side chain and 6'-position of the polyhydronaphthyl ring. Derivatives (I) and analogs thereof are useful in treating hypercholesterolemia. ##STR1##

  这项发明涉及新型中间体及其制备的新型过程，其中所述中间体在制备洛伐他汀（lovastation）及其类似物的5'-氧化衍生物（I）时是有用的，在聚氢萘环的8'-酰基侧链和6'-位置。衍生物（I）及其类似物在治疗高胆固醇血症方面是有用的。
• Process for the desilylation of a 4-silyloxy-tetrahydro-pyran-2-one
  申请人：Merck & Co., Inc.

  公开号：US05650523A1

  公开（公告）日：1997-07-22

  A process is described for the removal of a silyl protecting group from the 4-hydroxy group of a tetrahydro-pyran-2-one moiety.

  描述了一种从四氢吡喃-2-酮基团的4-羟基中去除硅保护基的过程。
• Novel synthesis of mevinolin-related compounds. Large-scale preparation of HMG-CoA reductase inhibitor L-679,336
  作者：Ann E. DeCamp、Sander G. Mills、Alan T. Kawaguchi、Richard Desmond、Robert A. Reamer、Lisa DiMichele、R. P. Volante

  DOI：10.1021/jo00011a022

  日期：1991.5

  A novel synthetic route to a mevinolin-related HMG-CoA reductase inhibitor L-679,336 is described. The key features of the synthesis are a diastereoselective osmium tetraoxide catalyzed dihydroxylation reaction and a highly selective, phosphorus-mediated, pinacol-type rearrangement to give ketone 6. In situ multinuclear NMR experiments were used to gain a detailed understanding of the pinacol step. The above route was used for multikilogram preparation of the title compound. Also described are Lewis acid catalyzed rearrangement reactions of epoxide intermediates 4 and 5, as well as the intramolecular hydrosilylation reaction of deacylated olefinic substrates 17 and 18.
• DUGGAN, MARK E.
  作者：DUGGAN, MARK E.

  DOI：——

  日期：——